The analysis of volatile organic compounds (VOCs) in exhaled human breath is rapidly emerging as a painless, non-invasive alternative to conventional methods of disease diagnosis and metabolite measurement. Breath VOC measurement is also commonly used for monitoring the effects of human exposure to environmental pollutants and drugs.
Hundreds of VOCs have been found in exhaled human breath, many of which originate from blood-air exchange in the lower (i.e. alveolar) area of the lungs. Because these compounds are mostly present at very small concentrations (parts-per-billion or less), their measurement by instruments such as GC-MS (Gas Chromatography-Mass Spectrometer) or infrared cavity-enhanced technologies often requires pre-concentration by filtering out undesired compounds such as nitrogen (N2) and oxygen (O2). The relatively large quantities of water vapour and carbon dioxide (CO2) present in exhaled breath should also be filtered out since they can hinder measurement of remaining VOCs in instruments such as GC-MS and IR spectrometers.
U.S. Pat. No. 5,465,728 to Philips discloses an Apparatus which is used to collect mammalian breath for chemical analysis and as a diagnostic tool for the physician. The Apparatus comprises a fluid reservoir container having first and second ends and a body extending between these ends so as to define an interior chamber; a breath entry portal; a breath exit portal; a sampling portal; a jacket to maintain the temperature of the chamber; a sample container for holding samples of exhaled breath; and pump means for moving selected samples of breath from the reservoir container into the sample container.
U.S. Pat. No. 6,726,637 also to Philips discloses an arrangement for the collection, concentration, and optional analysis of volatile organic components in alveolar breath that includes a condensation unit which removes water vapor from the alveolar breath. The arrangement has two significant shortcomings. The first is that the disclosed method for alveolar sampling is based on assumptions of the subject's lung capacity and expiration rate. The method is therefore subject to inaccuracies in cases where a particular subject's lung capacity and/or expiration rate deviates strongly from the normal assumptions. Furthermore, there is no discussion about how cross-contamination of VOCs between subjects is prevented or otherwise dealt with.
U.S. Pat. No. 6,582,376 to Baghdassarian discloses a device for collecting alveolar breath. Breath is expired into the inlet of a hollow body. The hollow body has two outlets, with a valve disposed in each outlet. The concentration of a specific gaseous component of expired breath is monitored by a gas concentration monitor as the expired breath passes through the hollow body to determine when alveolar breath is present in the hollow body. When alveolar breath is present in the hollow body, the valve in the second outlet is actuated to an open position to collect the alveolar breath in the collection reservoir affixed to the hollow body at the second outlet. While the Baghdassarian Apparatus employs a CO2-based method for discriminating between alveolar and tidal breath, it is unable to concentrate VOCs and is unable to remove undesired CO2 and water from the breath sample.
United States Patent Application Publication No. 2004/0162500 to Kline discloses a diagnosis method for respiratory disease based on the separation of the expired airway phase in an exhaled breath from the alveolar phase, and a device to accomplish the method. The device includes a cartridge assembly and a disposable condensing chamber carried in a substantially enclosed housing. The cartridge assembly includes a disposable cartridge and a reusable control system that monitors a characteristic of gas passing through the cartridge to determine when to divert the exhaled breath to an exhaust outlet and when to divert the exhaled breath to the condensing chamber. The characteristic is selected as being representative of the transition from the expired airway phase to the alveolar phase. Also included are a refrigeration system, an auxiliary monitoring system for determining when a sufficient volume of gas has been produced, and a built-in analyzer.
The Kline device contains a mechanism capable of diverting the non-alveolar component of breath from being collected and concentrated, based on the measurement of some characteristic of the exhaled breath passing through. However, the Kline Apparatus is designed to collect breath water vapour for subsequent analysis of the breath condensates found therein, and is not appropriate for applications where it is desirable to filter out such water and to concentrate remaining breath VOCs.